Discovery of a small molecule insulin mimetic with antidiabetic activity in mice

Insulin elicits a spectrum of biological responses by binding to its cell s urface receptor. In a screen for small molecules that activate the human in sulin receptor tyrosine kinase, a nonpeptidyl fungal metabolite (L-783,281) was identified that acted as an insulin mimetic in several biochemical and cellular assays. The compound was selective for insulin receptor versus in sulin-like growth factor I (IGFI) receptor and other receptor tyrosine kina ses. Oral administration of L-783,281 to two mouse models of diabetes resul ted in significant Lowering in blood glucose Levels. These results demonstr ate the feasibility of discovering novel insulin receptor activators that m ay Lead to new therapies for diabetes.